Keytruda Receives 2 New Indications: Metastatic Cervical Cancer and Relapsed Mediastinal Large B-Cell Lymphoma

August 2018, Vol 8, No 8 - FDA Approvals, News & Updates


On June 12, 2018, the FDA granted accelerated approval to pembrolizumab (Keytruda; Merck) for patients with recurrent or metastatic cervical cancer that progressed during or after chemotherapy and whose tumors express PD-L1, as determined by an FDA-approved test. Concurrently, the FDA approved the PD-L1 IHC 22C3 pharmDx kit as a companion diagnostic test for determining the PD-L1 status in this patient population.

This approval was based on 98 patients in the KEYNOTE-158 study who had recurrent or metastatic cervical cancer expressing PD-L1, as was determined by the PD-L1 IHC 22C3 pharmDx test. At a median of 11.7-month follow-up, the overall response rate was 14.3% among 77 patients whose tumors expressed PD-L1; of these responses, 2.6% were complete responses and 11.7% were partial responses.

Based on 11 patients who responded to treatment, the median duration of response was not reached at the time of this approval; the duration of response was ≥6 months in 91% of the patients. No responses were seen in patients without PD-L1 expression.

Serious adverse reactions were reported in 39% of patients, and pembrolizumab was discontinued in 8% of the patients because of adverse reactions.

A day later, on June 13, 2018, the FDA accelerated the approval of pembrolizumab for adult and pediatric patients with relapsed or refractory primary mediastinal large B-cell lymphoma (PMBCL). The FDA granted pembrolizumab orphan drug designation and breakthrough therapy designation for this indication.

This approval was based on results from the KEYNOTE-170 clinical trial of 53 patients with relapsed or refractory PMBCL. Patients received intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years, or until disease progression or unacceptable toxicity.

The overall response rate was 45%, with 11% complete responses and 34% partial responses. In the 9.7-month follow-up, the median duration of response was not reached. Pembrolizumab is not recommended for patients with PMBCL for whom cytoreductive therapy is crucial.

Adverse events led to pembroliz­umab discontinuation (8%) or in­terruption (15%), and systemic corticosteroid therapy was required in 25% of patients who had an adverse reaction. Serious adverse events were reported in 26% of patients.